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20 pages, 413 KB  
Review
Cancer Screening in Older Prison Populations: A Missed Opportunity?
by Natalie Austin and Emma Plugge
Soc. Sci. 2026, 15(2), 64; https://doi.org/10.3390/socsci15020064 - 26 Jan 2026
Abstract
The number of older women imprisoned is increasing around the world, leading to an increased demand on health and social care services within prisons. Imprisoned women are considered older by age 50 as they experience a disproportionate burden of cancer and disease. Access [...] Read more.
The number of older women imprisoned is increasing around the world, leading to an increased demand on health and social care services within prisons. Imprisoned women are considered older by age 50 as they experience a disproportionate burden of cancer and disease. Access to prison cancer screening programmes in prison should mirror access in the community; however, this is not always the case. The purpose of this scoping review is to systematically review the literature relating to enablers and barriers of cancer screening programmes in imprisoned older women. We performed a scoping review using the Arksey and O’Malley framework. Twelve studies were identified. Locations of studies varied across high-income countries. Enablers and barriers were identified within operational, personal, and accessibility categories. To improve mortality relating to cancer diagnosis it is vital that older imprisoned women are supported to access cancer screening. It was identified that older imprisoned women have different needs to other prison populations, and the barriers and enablers identified relate to staffing, communication, peer support, and processes to improve the experience of the older prison population. There is limited research in this area, and older women are a minority in a marginalized prison population. More research is needed to ensure the appropriate and effective development of cancer screening services. Full article
(This article belongs to the Special Issue Research on Prisons and Ageing)
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10 pages, 414 KB  
Article
Association Between Human Papillomavirus Vaccination and the Risk of Cervical Cancer and Precancerous Lesions in Israel: A Retrospective Cohort Study
by Gabriel Chodick and Myriam Strassberg
J. Clin. Med. 2026, 15(3), 995; https://doi.org/10.3390/jcm15030995 (registering DOI) - 26 Jan 2026
Abstract
Background: Human papillomavirus (HPV) infection is the necessary cause of almost all cervical cancers. HPV vaccination programs have been implemented worldwide, yet real-world evidence on vaccine effectiveness against invasive cervical cancer remains limited. Methods: We conducted a retrospective cohort study using [...] Read more.
Background: Human papillomavirus (HPV) infection is the necessary cause of almost all cervical cancers. HPV vaccination programs have been implemented worldwide, yet real-world evidence on vaccine effectiveness against invasive cervical cancer remains limited. Methods: We conducted a retrospective cohort study using synthetically generated data from a large health provider in Israel, including women who underwent a first Papanicolaou (Pap) test during 2014–2015. Their HPV-vaccination status before an index Pap test was obtained from computerized records. Incident cervical cancer and high-grade cervical pathology (cervical cancer, cervical intraepithelial neoplasia [CIN] 1–3, and carcinoma in situ) occurrence were examined through 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and fitted with propensity score weighting. Results: The cohort included 98,102 women, of whom 9198 (9.4%) were vaccinated against HPV before an index Pap test. While HPV-vaccinated women had a higher risk of cervical pathology compared with unvaccinated women, among women vaccinated before age 18, HPV vaccination was associated with a substantially lower, though not statistically significant, risk of cervical cancer (HR 0.28, 95% CI: 0.07–1.20, p = 0.087). Conclusions: In this large cohort, HPV vaccination was correlated with a higher risk of cervical pathology, likely reflecting residual confounding factors from sexual behavior and differential baseline risks of HPV infection. In contrast, vaccination during adolescence showed a marked trend toward a reduced risk of cervical cancer, consistent with international evidence that early vaccination, prior to HPV exposure, is the most effective preventative treatment. Full article
(This article belongs to the Section Epidemiology & Public Health)
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27 pages, 1579 KB  
Article
Quadra Sense: A Fusion of Deep Learning Classifiers for Mitosis Detection in Breast Cancer Histopathology
by Afnan M. Alhassan and Nouf I. Altmami
Diagnostics 2026, 16(3), 393; https://doi.org/10.3390/diagnostics16030393 - 26 Jan 2026
Abstract
Background/Objectives: The difficulties caused by breast cancer have been addressed in a number of ways. Since it is said to be the second most common cause of death from cancer among women, early intervention is crucial. Early detection is difficult because of [...] Read more.
Background/Objectives: The difficulties caused by breast cancer have been addressed in a number of ways. Since it is said to be the second most common cause of death from cancer among women, early intervention is crucial. Early detection is difficult because of the existing detection tools’ shortcomings in objectivity and accuracy. Quadra Sense, a fusion of deep learning (DL) classifiers for mitosis detection in breast cancer histopathology, is proposed to address the shortcomings of current approaches. It demonstrates a greater capacity to produce more accurate results. Methods: Initially, the raw dataset is preprocessed by using a normalization by means of color channel normalization (zero-mean normalization) and stain normalization (Macenko Stain Normalization), and the artifact can be removed via median filtering and contrast enhancement using histogram equalization; ROI identification is performed using modified Fully Convolutional Networks (FCNs) followed by the feature extraction (FE) with Modified InceptionV4 (M-IV4), by which the deep features are retrieved and the feature are selected by means of a Self-Improved Seagull Optimization Algorithm (SA-SOA), and finally, classification is performed using Mito-Quartet. Results: Ultimately, using a performance evaluation, the suggested approach achieved a higher accuracy of 99.2% in comparison with the current methods. Conclusions: From the outcomes, the recommended technique performs well. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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16 pages, 2416 KB  
Article
Colorectal Cancer in Brazil: Regional Disparities and Temporal Trends in Diagnosis and Treatment, 2013–2024
by Luiz Vinicius de Alcantara Sousa, Jean Henri Maselli-Schoueri, Laércio da Silva Paiva and Bianca Alves Vieira Bianco
Diseases 2026, 14(2), 40; https://doi.org/10.3390/diseases14020040 - 26 Jan 2026
Abstract
Background/Objectives: Colorectal cancer (CRC) is a major public health challenge in Brazil, characterized by marked regional disparities. Although national legislation mandates that treatment begin within 60 days after diagnosis, compliance remains inconsistent, particularly within the Unified Health System (SUS). This study aimed to [...] Read more.
Background/Objectives: Colorectal cancer (CRC) is a major public health challenge in Brazil, characterized by marked regional disparities. Although national legislation mandates that treatment begin within 60 days after diagnosis, compliance remains inconsistent, particularly within the Unified Health System (SUS). This study aimed to analyze the time to treatment initiation for colon (C18) and rectal (C20) cancer in Brazil from 2013 to 2024, assessing regional inequalities, temporal trends, and factors associated with treatment delays. Methods: We conducted an ecological study using secondary data from the Ministry of Health’s PAINEL-Oncologia platform, which integrates information from SIA/SUS, SIH/SUS, and SISCAN. Records of patients diagnosed with colon and rectal cancer (ICD-10 C18–C20) were evaluated. Temporal trends were analyzed using Joinpoint regression, and factors associated with delayed treatment initiation (>60 days) were identified through multiple logistic regression models. Results: Persistent discrepancies were observed between diagnostic and treatment trends from 2013 to 2024, with the Annual Percent Change (APC) for diagnosis exceeding that for treatment, particularly among adults aged 55–69 years. The Southeast and South regions accounted for over 70% of all diagnosed cases, starkly contrasting with the less than 25% in the North and Northeast. More than 50% of patients across all clinical stages initiated treatment after the legally mandated 60-day period. Women with rectal cancer had a 28% higher risk (RR = 1.28) of being diagnosed at stage IV. Chemotherapy was the predominant initial therapeutic modality, while the need for combined chemo-radiotherapy was associated with markedly elevated risk ratios for delay (e.g., RR = 26.53 for stage IV rectal cancer). Treatment initiation delays (>60 days) were significantly associated with residence in the North/Northeast regions, female sex (for rectal cancer), advanced-stage disease, and complex therapeutic regimens. Conclusions: The study demonstrates persistent regional inequalities and highlights a substantial mismatch between diagnostic capacity and therapeutic availability in Brazil. These gaps contribute to treatment delays and reinforce the need to strengthen and expand oncological care networks to ensure equitable access and improve outcomes, particularly in underserved regions. Full article
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18 pages, 3927 KB  
Systematic Review
Extracellular Vesicle Associated Proteomic Biomarkers in Breast Cancer: A Systematic Review and Meta-Analysis
by Nahad Al-Mahrouqi, Hasan Al-Sayegh, Shoaib Al-Zadjali and Aafaque Ahmad Khan
Cells 2026, 15(3), 231; https://doi.org/10.3390/cells15030231 - 26 Jan 2026
Abstract
Breast cancer continues to be the most frequently diagnosed cancer among women worldwide and remains a leading cause of cancer-related mortality. Despite advances in imaging and biopsy-based approaches, current diagnostic methods are invasive, costly, and often insufficient to capture the molecular heterogeneity of [...] Read more.
Breast cancer continues to be the most frequently diagnosed cancer among women worldwide and remains a leading cause of cancer-related mortality. Despite advances in imaging and biopsy-based approaches, current diagnostic methods are invasive, costly, and often insufficient to capture the molecular heterogeneity of tumors. Extracellular vesicles (EVs) have emerged as promising non-invasive biomarkers owing to their role in intercellular communication and their enrichment with tumor-specific cargo. This study conducted a systematic review and meta-analysis of published literature to investigate proteomic alterations in EVs derived from breast cancer samples. From an initial 1097 records screened, four eligible studies were identified, reporting 628 differentially expressed proteins, of which 38 were consistently observed across multiple datasets. Functional enrichment analyses revealed predominant localization of these proteins to vesicle-associated compartments and significant involvement in biological processes related to cell growth, immune regulation, and tumor progression. Pathway analysis further highlighted integrin-mediated interactions, platelet activation, and hemostasis pathways as key molecular mechanisms represented within breast cancer EVs. Overall, the findings reveal a distinct EV proteomic signature in breast cancer that could support early detection and patient monitoring through minimally invasive testing. Future large-scale and standardized studies are needed to validate these candidate proteins and advance EV proteomics toward clinical application in breast cancer management. Full article
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13 pages, 736 KB  
Article
Access to Fertility Preservation Counselling for Young Women with Haematological Malignancies: Incidence-Adjusted Trends from the Italian PreFerIta Network (2015–2023)
by Renato Seracchioli, Michele Miscia, Diego Raimondo, Rossella Vicenti, Valentina Immediata, Annamaria Baggiani, Gianluca Gennarelli, Rocco Rago, Cristina Fabiani, Gemma Paciotti, Roberta Corno, Paola Anserini, Claudia Massarotti, Enrico Papaleo, Valeria Stella Vanni, Edgardo Somigliana, Francesca Filippi, Giulia Scaravelli, Lucia Speziale, Simone Bolli and Roberto De Lucaadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(3), 960; https://doi.org/10.3390/jcm15030960 (registering DOI) - 25 Jan 2026
Abstract
Background: Preserving fertility in young women with cancer is crucial for comprehensive care. Based on GBD 2023 estimates, approximately 1000 women aged 15–39 are diagnosed with haematological malignancies annually in Italy. Guidelines recommend timely fertility preservation (FP) counselling for all at-risk patients, yet [...] Read more.
Background: Preserving fertility in young women with cancer is crucial for comprehensive care. Based on GBD 2023 estimates, approximately 1000 women aged 15–39 are diagnosed with haematological malignancies annually in Italy. Guidelines recommend timely fertility preservation (FP) counselling for all at-risk patients, yet real-world access data remain limited. Methods: This multicentre, retrospective observational study analysed FP counselling for women aged 15–39 with haematological malignancies from 2015 to 2023. Counselling data were extracted from the Italian Assisted Reproductive Technology Registry (IARTR). This data collection system, known as PreFerIta, was developed within a project supported by the Italian Ministry of Health to collect data on Fertility Preservation (FP) treatments in oncology patients and/or those at risk of iatrogenic infertility, provided in seven specialised ART centres across Italy. The PreFerIta database includes data on both oocyte cryopreservation and ovarian tissue cryopreservation. Annual visits were related to the estimated regional incidence of new haematological malignancies (GBD 2023). Counselling-to-incidence ratios, absolute/relative gaps, and 95% confidence intervals (CIs) were calculated. Results: From 2015 to 2023, an estimated 4473 new haematological malignancies occurred in the catchment regions. Concurrently, 1200 FP counselling visits were recorded. While incidence modestly declined, counselling activity remained high. The counselling-to-incidence ratio increased from 17.33% in 2015 to 31.92% in 2018, stabilising between 26% and 31% thereafter (30.98% in 2023). The relative counselling gap decreased from 82.67% to 69.02%. These ratios represent lower-bound estimates of access to specialised oncofertility consultations. Conclusions: In this Italian network, approximately one in four to one in three incident haematological malignancies in young women were associated with specialised FP counselling. This reflects a substantial integration of oncofertility services into haematology care, highlighting opportunities to further strengthen referral pathways and achieve full guideline concordance. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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33 pages, 2702 KB  
Review
Beneficial Effects of Fisetin, a Senotherapeutic Compound, in Women’s Reproductive Health and Diseases: Evidence from In Vitro to Clinical Studies
by Samya El Sayed, D’leela Saiyed, Valeria I. Macri, Awurakua Asamoah-Mensah, James H. Segars and Md Soriful Islam
Nutrients 2026, 18(3), 393; https://doi.org/10.3390/nu18030393 - 25 Jan 2026
Abstract
Fisetin is a naturally occurring flavonoid, a type of polyphenol found in fruits and vegetables such as strawberries, apples, persimmons, and onions. It has gained increasing attention for its antioxidant properties (enhancement of SOD1 and CAT activity and reduction of ROS), anti-inflammatory effects [...] Read more.
Fisetin is a naturally occurring flavonoid, a type of polyphenol found in fruits and vegetables such as strawberries, apples, persimmons, and onions. It has gained increasing attention for its antioxidant properties (enhancement of SOD1 and CAT activity and reduction of ROS), anti-inflammatory effects (suppression of NF-κB signaling), and senotherapeutic activity (senolytic and senomorphic effects). Although numerous studies have examined fisetin in the context of aging and chronic diseases, its role in women’s reproductive health has not been systematically explored. Mechanistically, fisetin regulates several pathophysiological processes, including ovarian aging, fibrosis, angiogenesis, and hormonal regulation, suggesting its potential relevance to female reproductive health and disease. Indeed, emerging evidence indicates that fisetin may support ovarian function and hormonal balance, modulate fibrosis and metabolism in benign gynecologic conditions, and suppress cell growth in gynecologic cancers. Early-phase clinical studies in non-gynecologic conditions suggest an acceptable safety profile, although evidence in reproductive health remains absent. This review summarizes current experimental and clinical evidence, identifies critical gaps in mechanistic understanding, and discusses future directions for advancing fisetin as a promising non-hormonal therapeutic option in reproductive health and diseases. Full article
(This article belongs to the Special Issue Linking Fruit and Vegetable Bioactives to Human Health and Wellness)
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16 pages, 1766 KB  
Article
Antitumor Activity of the ACC Inhibitor Firsocostat in Breast Cancer Cell Lines: A Proof-of-Concept In Vitro Study
by Simona Picerno, Eugenia Giglio, Martina Giuseffi, Marcello Radino, Marzia Sichetti and Marisabel Mecca
Pharmaceuticals 2026, 19(2), 201; https://doi.org/10.3390/ph19020201 - 24 Jan 2026
Viewed by 46
Abstract
Background/Objectives: Breast cancer is the most frequently diagnosed malignancy among women and is characterized by marked heterogeneity in treatment response. Metabolic reprogramming, particularly enhanced de novo lipogenesis, represents a hallmark of cancer progression and a promising therapeutic target. Firsocostat, a selective allosteric [...] Read more.
Background/Objectives: Breast cancer is the most frequently diagnosed malignancy among women and is characterized by marked heterogeneity in treatment response. Metabolic reprogramming, particularly enhanced de novo lipogenesis, represents a hallmark of cancer progression and a promising therapeutic target. Firsocostat, a selective allosteric inhibitor of acetyl-CoA carboxylase (ACC), has previously been investigated in metabolic diseases but has never been evaluated in breast cancer models. This study aimed to assess the antitumor effects of firsocostat on breast cancer cell lines. Methods: We investigated the cytotoxic and metabolic effects of firsocostat in four breast cancer cell lines—MCF7 (luminal A HR+), SK-BR-3 (HER2-positive), MDA-MB-231 (triple-negative), and HCC1937 (triple-negative, BRCA1-mutated)—together with the non-tumorigenic MCF-10A line. Dose- and time-dependent responses were evaluated using phase-contrast microscopy for morphological evaluation, Trypan Blue exclusion assays, and MTS-based viability assays. Results: Firsocostat significantly reduced cell viability across all breast cancer subtypes in a concentration- and time-dependent manner, with IC50 values ranging from 80 to 93 µM. In contrast, non-tumorigenic MCF-10A cells were less affected, indicating a selective cytotoxic effect toward malignant cells. Conclusions: Firsocostat exerts robust cytotoxic effects in breast cancer models, identifying it as a promising metabolism-targeting therapeutic candidate capable of selectively impairing breast cancer cell survival by disrupting fatty acid biosynthesis. These results indicate that firsocostat could represent a viable candidate as a metabolic-based therapeutic approach for breast cancer. Given its established clinical safety profile in metabolic diseases, firsocostat warrants further preclinical investigation and supports further mechanistic and preclinical evaluation. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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17 pages, 3526 KB  
Article
Spectral Precision: The Added Value of Dual-Energy CT for Axillary Lymph Node Characterization in Breast Cancer
by Susanna Guerrini, Giulio Bagnacci, Paola Morrone, Cecilia Zampieri, Chiara Esposito, Iacopo Capitoni, Nunzia Di Meglio, Armando Perrella, Francesco Gentili, Alessandro Neri, Donato Casella and Maria Antonietta Mazzei
Cancers 2026, 18(3), 363; https://doi.org/10.3390/cancers18030363 - 23 Jan 2026
Viewed by 93
Abstract
Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age, [...] Read more.
Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age, 65 years; 111 women and 6 men) who underwent DECT followed by axillary lymphadenectomy between April 2015 and July 2023, were analyzed. A total of 375 lymph nodes (180 metastatic, 195 benign) were evaluated. Two radiologists recorded morphological criteria (adipose hilum status, cortical appearance, extranodal extension, and short-axis diameter) and placed regions of interest to measure dual-energy parameters: attenuation at 40 and 70 keV, iodine concentration, water concentration and spectral slope. Normalized iodine concentration was calculated using the aorta as reference. Univariate analysis identified variables associated with metastasis. Multivariate logistic regression with cross-validation was used to construct two models: one based solely on morphological features and one integrating water concentration. Results: On univariate testing, all DECT parameters and morphological criteria differed significantly between metastatic and benign nodes (p < 0.01). In multivariate analysis, water concentration emerged as the only independent DECT predictor (odds ratio = 0.97; p = 0.002) alongside cortical abnormality, absence of adipose hilum, extranodal extension and short-axis diameter. The morphologic model achieved an area under the receiver operating characteristic curve (AUC) of 0.871. Increasing water concentration increased the AUC to 0.883 (ΔAUC = 0.012; p = 0.63, not significant), with internal cross-validation confirming stable performance. Conclusions: A model combining standard morphologic criteria with water concentration quantification on DECT accurately differentiates metastatic from benign axillary nodes in BC patients. Although iodine-based metrics remain valuable indicators of perfusion, water concentration offers additional tissue composition information. Future multicenter prospective studies with standardized imaging protocols are warranted to refine parameter thresholds and validate this approach for routine clinical use. Full article
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15 pages, 3380 KB  
Systematic Review
Re-Evaluating the Progesterone Challenge Test as a Physiologic Marker of Endometrial Cancer Risk: A Systematic Review and Meta-Analysis
by Rachel J. Woima, Derek S. Chiu, Elise Abi Khalil, Sabine El-Halabi, Andrea Neilson, Laurence Bernard, Jessica N. McAlpine and Aline Talhouk
Diagnostics 2026, 16(3), 378; https://doi.org/10.3390/diagnostics16030378 - 23 Jan 2026
Viewed by 148
Abstract
Background/Objectives: With the rising incidence of obesity-related endometrial cancer, there is renewed interest in physiologic, low-cost approaches to identify women with hormonally active endometrium who may benefit from early preventive interventions. The progesterone challenge test (PCT), an established clinical tool for evaluating [...] Read more.
Background/Objectives: With the rising incidence of obesity-related endometrial cancer, there is renewed interest in physiologic, low-cost approaches to identify women with hormonally active endometrium who may benefit from early preventive interventions. The progesterone challenge test (PCT), an established clinical tool for evaluating amenorrhea, has been previously proposed as a method to detect endometrial pathology. This study systematically evaluated the diagnostic accuracy of the PCT for detecting endometrial hyperplasia, intraepithelial neoplasia, and carcinoma in asymptomatic postmenopausal women to determine its potential role as a physiologic marker of endometrial cancer risk. Methods: A systematic review and meta-analysis were conducted following PRISMA-DTA guidelines. MEDLINE, EMBASE, EBM Reviews, and CINAHL were searched from inception to 20 January 2025, along with ClinicalTrials.gov and grey literature. Eligible studies prospectively evaluated the PCT with endometrial biopsy as the reference standard. Data extraction and risk-of-bias assessment were performed in duplicate. Risk of bias was assessed using QUADAS-2. Pooled sensitivity, specificity, and predictive values were estimated using hierarchical summary receiver operating characteristic models. Results: Nineteen studies (n = 3902) met the inclusion criteria. The pooled sensitivity and specificity of the PCT for detecting endometrial pathology were 95% (95% CI 86–100%) and 87% (76–96%), respectively. The positive predictive value was 32% (95% CI, 16–50%) and the negative predictive value was 100% (100–100%). When endometrial proliferation was included in the target condition, sensitivity decreased to 82%, but positive predictive value increased to 70%. Conclusions: The PCT shows high diagnostic accuracy for identifying estrogen-driven endometrial pathology in asymptomatic postmenopausal women. Re-evaluating this simple, physiologic test as a functional risk-stratification tool could inform precision prevention strategies for endometrial cancer. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Endometrial Diseases)
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23 pages, 606 KB  
Article
An Intelligent Hybrid Ensemble Model for Early Detection of Breast Cancer in Multidisciplinary Healthcare Systems
by Hasnain Iftikhar, Atef F. Hashem, Moiz Qureshi, Paulo Canas Rodrigues, S. O. Ali, Ronny Ivan Gonzales Medina and Javier Linkolk López-Gonzales
Diagnostics 2026, 16(3), 377; https://doi.org/10.3390/diagnostics16030377 - 23 Jan 2026
Viewed by 86
Abstract
Background/Objectives: In the modern healthcare landscape, breast cancer remains one of the most prevalent malignancies and a leading cause of mortality among women worldwide. Early and accurate prediction of breast cancer plays a pivotal role in effective diagnosis, treatment planning, and improving survival [...] Read more.
Background/Objectives: In the modern healthcare landscape, breast cancer remains one of the most prevalent malignancies and a leading cause of mortality among women worldwide. Early and accurate prediction of breast cancer plays a pivotal role in effective diagnosis, treatment planning, and improving survival outcomes. However, due to the complexity and heterogeneity of medical data, achieving high predictive accuracy remains a significant challenge. This study proposes an intelligent hybrid system that integrates traditional machine learning (ML), deep learning (DL), and ensemble learning approaches for enhanced breast cancer prediction using the Wisconsin Breast Cancer Dataset. Methods: The proposed system employs a multistage framework comprising three main phases: (1) data preprocessing and balancing, which involves normalization using the min–max technique and application of the Synthetic Minority Over-sampling Technique (SMOTE) to mitigate class imbalance; (2) model development, where multiple ML algorithms, DL architectures, and a novel ensemble model are applied to the preprocessed data; and (3) model evaluation and validation, performed under three distinct training–testing scenarios to ensure robustness and generalizability. Model performance was assessed using six statistical evaluation metrics—accuracy, precision, recall, F1-score, specificity, and AUC—alongside graphical analyses and rigorous statistical tests to evaluate predictive consistency. Results: The findings demonstrate that the proposed ensemble model significantly outperforms individual machine learning and deep learning models in terms of predictive accuracy, stability, and reliability. A comparative analysis also reveals that the ensemble system surpasses several state-of-the-art methods reported in the literature. Conclusions: The proposed intelligent hybrid system offers a promising, multidisciplinary approach for improving diagnostic decision support in breast cancer prediction. By integrating advanced data preprocessing, machine learning, and deep learning paradigms within a unified ensemble framework, this study contributes to the broader goals of precision oncology and AI-driven healthcare, aligning with global efforts to enhance early cancer detection and personalized medical care. Full article
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23 pages, 497 KB  
Systematic Review
The Contribution of Genetic Modifiers to Ovarian Cancer Risk in BRCA1 and BRCA2 Pathogenic Variant Carriers
by Dagmara Cylwik, Roksana Dwornik and Katarzyna Białkowska
Cancers 2026, 18(3), 354; https://doi.org/10.3390/cancers18030354 - 23 Jan 2026
Viewed by 199
Abstract
The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease [...] Read more.
The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease penetrance (BRCA1: ~40% and BRCA2: 11–27%), substantial variability in individual risk is observed, suggesting the influence of additional genetic variants. Background: Ovarian cancer is characterized by late detection and high mortality, and a significant portion of risk among BRCA1/2 carriers is shaped by reproductive and environmental factors as well as genetic modifiers. The article emphasizes that carriers of the same BRCA PV can exhibit markedly different risk levels depending on additional variants that modulate key biological processes, such as DNA repair, cell cycle regulation, and apoptosis. Methods: A systematic literature search covering the years 1996–2025 was conducted in the PubMed database. Initially, 734 publications were identified; after removing duplicates, thematically irrelevant articles, non-full-text papers, and studies not meeting the inclusion criteria, 47 articles were included in the review. These studies covered candidate gene analyses, GWAS, and data from the CIMBA consortium, which enables the examination of large cohorts of PV carriers. Results: The review identified numerous variants associated with increased or decreased ovarian cancer risk in BRCA1 carriers, including the following: OGG1, DR4, MDM2, CYP2A7, CASP8, ITGB3, HRAS1, TRIM61, and MTHFR. The reviewed studies also identified both protective and risk-increasing variants among BRCA2 PV carriers: UNG, TDG, and PARP2, and haplotypes in ATM, BRIP1, BARD1, MRE11, RAD51, and 9p22.2. The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP. Protective variants include BNC2 and LINC00824. The only SNP reaching genome-wide significance (p < 5 × 10−8) was in BNC2. Conclusions: The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets. Full article
(This article belongs to the Special Issue Genetics of Ovarian Cancer (2nd Edition))
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25 pages, 5025 KB  
Article
Synergistic Anticancer Activity of Annona muricata Leaf Extract and Cisplatin in 4T1 Triple-Negative Breast Cancer Cells
by Oumayma Kouki, Mohamed Montassar Lasram, Amel Abidi, Jérôme Leprince, Imen Ghzaiel, John J. Mackrill, Taoufik Ghrairi, Gérard Lizard and Olfa Masmoudi-Kouki
Cells 2026, 15(3), 213; https://doi.org/10.3390/cells15030213 - 23 Jan 2026
Viewed by 215
Abstract
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although cisplatin is widely used in chemotherapy, its clinical efficacy is often limited by adverse effects and resistance. Thus, natural bioactive compounds are gaining attention as complementary therapeutic agents. [...] Read more.
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although cisplatin is widely used in chemotherapy, its clinical efficacy is often limited by adverse effects and resistance. Thus, natural bioactive compounds are gaining attention as complementary therapeutic agents. This study aimed to evaluate the anti-tumor effects of Annona muricata leaf extract on murine breast cancer 4T1 cells, used alone or in combination with cisplatin. Cisplatin induced intrinsic apoptosis through mitochondrial membrane disruption, up-regulation of the Bax gene and inhibition of the PI3K/AKT/mTOR signaling pathway. Cisplatin also promoted hypoxia by HIF1α gene expression, inflammation by TNFα and IL-6 gene expression, and induced cell cycle arrest at the sub-G1 phase by down-regulation of cyclin D1 and cyclin E1 genes. Annona muricata leaf extract triggered autophagy-mediated 4T1 cell death through mainly mTOR down-regulation and increased expression of Beclin1 and LC3 genes. It also induced cell cycle arrest at sub-G1 and S phases in a concentration- and time-dependent manner. When, combined with cisplatin, Annona muricata extract shifts the cell death pathway from intrinsic apoptosis toward autophagy by reduced caspase-3 gene expression and activity and enhanced LC3-I to LC3-II conversion. Moreover, Annona muricata extract attenuated cisplatin-induced inflammation by inhibiting TNFα and IL-6 gene expression and reinforced cell cycle arrest through suppression of the cyclin D1 gene. In conclusion, our results suggest that Annona muricata leaf extract exerts significant anti-tumor activity in breast cancer cells and may enhance cisplatin efficacy by shifting the signaling pathway from intrinsic apoptosis toward autophagy, and attenuating inflammation-related effects, supporting its potential use as a complementary therapeutic strategy. Full article
(This article belongs to the Section Cellular Pathology)
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13 pages, 262 KB  
Review
Achieving Pregnancy After Early Hormone Receptor-Positive Breast Cancer: Recent Evidence and Clinical Considerations
by Karine E. Ronan and Janice M. Walshe
Cancers 2026, 18(2), 348; https://doi.org/10.3390/cancers18020348 - 22 Jan 2026
Viewed by 58
Abstract
An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence [...] Read more.
An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence on pregnancy after early HR+ breast cancer, with particular emphasis on prospective data from the POSITIVE trial. We examine the safety of temporary endocrine therapy interruption, the impact of assisted reproductive technologies (ART) in achieving pregnancy, breastfeeding feasibility and impact, hormonal predictors of fertility, pregnancy outcomes and considerations for special populations, including BRCA mutation carriers. Retrospective studies have suggested no adverse survival impact associated with pregnancy after breast cancer. The POSITIVE trial provides prospective evidence that temporary interruption of endocrine therapy to attempt pregnancy does not increase short-term recurrence risk in selected patients. Approximately three-quarters of participants achieved pregnancy. Fertility preservation and ART were commonly used and were not associated with worse short-term oncologic outcomes. Biomarkers such as anti-Müllerian hormone offer supportive but imperfect prediction of fertility potential. Breastfeeding was feasible for many women and did not adversely affect breast cancer outcomes. Available data among BRCA mutation carriers are reassuring but largely observational. Current evidence supports the safety and feasibility of pregnancy after early HR+ breast cancer in carefully selected patients. However, longer follow-up, inclusion of higher-risk populations, and evaluation of newer therapies are needed. Individualized, multidisciplinary counselling remains central to informed decision-making. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
19 pages, 1597 KB  
Review
Natural Phytochemicals as Inhibitors of HIF-1α in Breast Cancer: Review of Preclinical Evidence and Future Prospects
by Ivan Dam, Eric Liu, Abida Ali, Chikezie O. Madu and Yi Lu
Curr. Issues Mol. Biol. 2026, 48(1), 121; https://doi.org/10.3390/cimb48010121 - 22 Jan 2026
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Abstract
Breast cancer is the most prevalent form of cancer among women globally. The hypoxic microenvironment resulting from the rapid oxygen consumption of rapidly dividing cancer cells causes the accumulation of hypoxia-inducible factor-1α (HIF-1α) due to reduced catalytic activity of prolyl hydroxylase domain 2 [...] Read more.
Breast cancer is the most prevalent form of cancer among women globally. The hypoxic microenvironment resulting from the rapid oxygen consumption of rapidly dividing cancer cells causes the accumulation of hypoxia-inducible factor-1α (HIF-1α) due to reduced catalytic activity of prolyl hydroxylase domain 2 (PHD2) and Von Hippel-Lindau (VHL). Under physiological conditions, HIF-1α regulates cell response to hypoxic environments. Activating genes are involved in glycolysis, angiogenesis, and erythropoiesis. However, the sustained hypoxic environment in breast cancer facilitates metastasis, immune evasion, and drug resistance. Consequently, HIF-1α is a key target in breast cancer treatment, and such inhibitors of HIF-1α may prove to be a viable treatment option. Increasing evidence suggests that natural chemicals, such as polyphenols, isothiocyanates, curcumin, and alkaloids, are inhibitors of HIF-1α. Preclinical studies using animal models and breast cancer cell lines indicate significant reductions in angiogenesis, despite challenges of heterogeneity, bioavailability, and dose optimization. This review intends to summarize current evidence on natural inhibitors of HIF-1α and potential future studies. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment: 2nd Edition)
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